Grant: Master's Award: Canada Graduate Research Scholarships - Master's program

Heart failure (HF) caused by chronic pressure overload is now recognized as a systemic disease involving metabolic dysfunction, inflammation, and disruptions in gut–heart communication. Our lab has shown that the adiponectin receptor agonist ALY688 improves cardiac hypertrophy, fibrosis, and metabolic injury in pressure-overload models. ALY688 also reduces several gut-derived metabolites, suggesting that changes in microbial signaling may contribute to its cardioprotective effects. This leads to a central question: how does ALY688 influence upstream gut-derived pathways that affect the heart? To explore this connection, the proposed research focuses on bacterial extracellular vesicles (BEVs), small particles released by gut microbes that cross the intestinal barrier and circulate systemically. Because BEVs carry lipids, metabolites, and microbial DNA, they can shape inflammation, mitochondrial function, and lipid metabolism in distant organs. However, their role in pressure-overload HF, and whether ALY688 alters their abundance or cargo, remains unknown. Using a transverse aortic constriction (TAC) mouse model, we will compare Sham, TAC, and TAC+ALY688 groups. Longitudinal fecal, portal, and serum samples will be used to isolate and characterize BEVs through nanoparticle tracking analysis and electron microscopy. Cargo profiling will assess metabolites, LPS content, and microbial DNA. In parallel, we will evaluate cardiac function, gut permeability, inflammation, and tissue-level metabolomics to connect microbial changes with cardiac outcomes. By defining how ALY688 reshapes gut-derived vesicle signals, this project aims to identify new biomarkers and therapeutic targets for pressure-overload HF and clarify how the gut communicates with the heart.